The overarching goals of this RO1 application are to study the clinical epidemiology and pathogenesis of retroviral, opportunistic and tropical infections of the nervous system in Peru, building on research collaborations and investigations initiated during the R21 grant entitled "Central Nervous System Infections in Peru"; and to continue development of neurologist investigators in academic and research institutions in selected cities throughout Peru. The specific aims of this grant are to 1) define the risk determinants and clinical manifestations of HTLV-II, HTLV-I, HIV infections and of coinfections with two or more of these three retroviral pathogens in the four largest cities in Peru; 2) establish a national reference center for clinical research on HTLV infection for conduct of cohort studies of the natural history, clinical manifestations, and pathogenesis of HTLV-I and -II infections in persons referred from blood banks; and 3) examine the influence of these three retroviral infections on the natural history of opportunistic and tropical infections of the CNS in persons with retroviral infection. During our R21 planning grant, we discovered that HTLV-II infection was unexpectedly prevalent in selected populations in Lima (the capital) and two of the largest cities in the Amazon Jungle. In addition, we developed research collaborations with neurologists in Lima (the capital), Iquitos (Jungle), Arequipa (Andes Mountains), and Trujillo (Coast), and determined the most common manifestations of neuroAIDS in Iquitos and Arequipa; and through conferences and in-country training, provided research and human subjects training to over 200 experienced and new clinical investigators - many of them neurologists. Concurrently, UW-led HIV/AIDS-related research funding in Peru has grown to $5,000,000 per year from NIH and from private foundations, providing an outstanding foundation for further development of a CNS retroviral research program. The Collaborative Network for Tropical Neurologic Infectious Diseases established with researchers in nongovernmental and Ministry of Health institutions in Peru, with the U.S. Naval Medical Research Center Detachment (NMRCD) in Peru, and with Universities in Peru and the United States, will support future research on the clinical epidemiology of retroviral infections and their interactions with emerging tropical infections in Peru and eventually the Andean Region. In addition to continuing our investigations, we plan to continue training activities to address the research, education, training, and mentoring needs and opportunities related to CNS infection identified during the R21 planning grant.